PROJECT SUMMARY/ABSTRACT Resource Project Discovering the functions of the tens of thousands of genes in the human genome is a required step for understanding human biology and disease. Genetic model organisms, including zebrafish, play a critical role in this discovery process, because genetic analysis can connect gene sequence and function. Model organism databases, like ZFIN, provide tools required to make this connection. The zebrafish has emerged as a premier organism to study vertebrate biology. Powerful techniques allow rapid efficient generation and recovery of mutations affecting genes that orchestrate developmental patterning, organogenesis, physiology, and behavior. It is easy to study gene function by generating transgenic zebrafish, by knocking down gene function with morpholino antisense oligonucleotides, or by altering gene function by genome editing. The genome has been sequenced and about 50% of the protein coding genes have been mutated by targeted gene knockout technology. Large-scale projects are underway or planned that will produce functional data about almost all the genes and sequence-based functional elements in the genome. Multiple mutations and gene knockdowns can be combined in the same individual to study gene modifiers and other genetic interactions. The functions of most of these genes are conserved among vertebrate groups. Thus, analysis of zebrafish mutations provides insights into gene functions in other vertebrates, including humans. The long term goals for ZFIN are a) to be the community database resource for the laboratory use of zebrafish, b) to develop and support integrated zebrafish genetic, genomic, developmental, and physiological information, c) to maintain the definitive reference data sets of zebrafish research information, d) to link this information extensively to corresponding data in other model organism and human databases, e) to facilitate the use of zebrafish as a model for human biology, and f) to help serve the broad needs of the biomedical research community. In this part of the project, we will curate and integrate zebrafish research data into the ZFIN database and link them to human biology and disease, and we will develop maintain the zebrafish reference genome and provide ongoing annotation. We will also continue to improve zebrafish gene models.